The biotechnology industry uses different manufacturing systems for creating aseptic and sterile connections between process containers and equipment, such as plastic bags and pumps. A known manufacturing system uses controlled environments such as clean rooms or cabinets to ensure aseptic connections during manufacture. When necessary connections are made in such a controlled environment that breaches sterile tubing and piping, the environment does not contaminate the fluid flow passage. However, maintaining a clean room is time consuming, difficult and costly to validate.
Another known manufacturing system uses disposable plastic bags connected to flexible thermoplastic tubing, which requires special connections to assure that the bags and tubes remain clean and sterile. A sterile tube welding machine can be used to weld the thermoplastic tubing in a sterile manner without the need for a clean room, a laminar flow cabinet or similar environmental control device. After the thermoplastic tubes cool, a sterile weld is formed. A tube welding machine is however also usually limited in applicability to specific tube size and materials, such as thermoplastic tubing. Furthermore, tube welding machines are typically large, heavy, lack versatility, and expensive. Known are also pre-sterile bags and tube sets which can be supplied with the appropriate disposable aseptic connection system fittings already in place. These, connections are simple, repeatable and validatable. Single use systems, also called disposable systems, are more and more used in the bioprocess industry. For example separation or reaction systems such as chromatography systems, filter systems or bioreactor systems have today at least partly been provided as disposable systems. This eliminates the need for cleaning and cleaning validation before processing, in between processes and cycles or after processing before re-use as required for conventional re-usable equipment. With disposable systems cross-contamination is avoided.
Bioburden control of single-use equipment during manufacturing of the equipment itself is required to eliminate cleaning needs before bringing single-use equipment into product contact. This is usually achieved by manufacturing of single-use equipment in controlled environment (clean room), often followed by sterilization processes (gamma irradiation). The demands of the level of bioburden control can differ for different applications. However, bioburden control to a certain degree of the equipment is not only required for some applications, but also considered as the preferable for most of the applications using disposable equipment. The production of this equipment in controlled environments is required to guarantee a low initial level of contaminants prior to the bioburden control procedure. Sterility and asepsis are terms used to define the state of a system, a piece of equipment or a fluid conduit as being in control of bioburden levels to different degrees.
Prior art describes varying apparatus for accomplishing sterile connections using disposable aseptic connectors. Typically the sterility of the connector before establishment of connection is ensured by a releasably bonded cover film which can be removed together with the cover film of a mating connector when they are connected or at a close distance to each other. Such connectors have been described in e.g. U.S. Pat. No. 6,679,529, WO 2009/002468 and WO 2013/147688, which are hereby incorporated by reference in their entireties. They are also commercially available from GE Healthcare under the name of ReadyMate™.
The connectors described above have to be facing each other in particular directions to allow connection, in that the cover films of both connectors have to be pulled out together in the same direction. As the connectors are also fixed at one end to the tubing, it is an issue that the tubing with the connectors may have to be twisted to allow connection. This is undesirable, particularly when complex bioprocessing equipment is to be connected with large diameter tubing.
Accordingly there is a need for connectors that do not require twisting of the tubing.